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http://asiair.asia.edu.tw/ir/handle/310904400/8205
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| Title: | KEAP1 E3 Ligase-Mediated Downregulation of NF-kappa B Signaling by Targeting IKK beta |
| Authors: | Lee, DF (Lee, Dung-Fang);Kuo, HP (Kuo, Hsu-Ping);Liu, M (Liu, Mo);Chou, CK (Chou, Chao-Kai);Xia, WY (Xia, Weiya);Du, Y (Du, Yi);Shen, J (Shen, Jia);Chen, CT (Chen, Chun-Te);Huo, L (Huo, Longfei);Hsu, MC (Hsu, Ming-Chuan);Li, CW (Li, Chia-Wei);Ding, QQ (Ding, Qingqing);Liao, TL (Liao, Tsai-Lien);Lai, CC (Lai, Chien-Chen);Lin, AC (Lin, Ann-Chi);Chang, YH (Chang, Ya-Hui);Tsai, SF (Tsai, Shih-Feng);Li, LY (Li, Long-Yuan);Hung, MC (Hung, Mien-Chie) |
| Contributors: | Department of Biotechnology |
| Keywords: | TUMOR ANGIOGENESIS;BREAST-CANCER;LUNG-CANCER;NRF2;INFLAMMATION;ACTIVATION;SUBSTRATE;PATHWAY;COMPLEX;PROTEIN |
| Date: | 2009-10 |
| Issue Date: | 2010-03-26 02:29:01 (UTC+0) |
| Publisher: | Asia University |
| Abstract: | I kappa B kinase beta (IKK beta) is involved in tumor development and progression through activation of the nuclear factor (NF)-kappa B pathway. However, the molecular mechanism that regulates IKK beta degradation remains largely unknown. Here, we show that a Cullin 3 (CUL3)-based ubiquitin ligase, Kelch-like ECH-associated protein 1 (KEAP1), is responsible for IKK beta ubiquitination. Depletion of KEAP1 led to the accumulation and stabilization of IKK beta and to upregulation of NF-kappa B-derived tumor angiogenic factors. A systematic analysis of the CUL3, KEAP1, and RBX1 genomic loci revealed a high percentage of genome loss and missense mutations in human cancers that failed to facilitate IKK beta degradation. Our results suggest that the dysregulation of KEAP1-mediated IKK beta ubiquitination may contribute to tumorigenesis. |
| Relation: | MOLECULAR CELL 36 (1): 131-140 |
| Appears in Collections: | [生物科技學系] 期刊論文
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